title: Low prevalence of germline PALB2 mutations in Australian triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) is a tumour classification that is defined by oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 receptor negativity. TNBCs share a similar gene expression profile to BRCA-mutated tumours, have been shown to carry a high proportion of BRCA mutations and have a more adverse prognosis compared to other types of breast tumours. PALB2 has been shown to be a moderate-penetrance breast cancer susceptibility gene and is involved in the same DNA damage repair pathway as BRCA1 and BRCA2; this raises the possibility that germline PALB2 mutations may be involved in the pathogenesis of TNBCs. In our study, we sequenced the coding regions of PALB2 (including intron/exon boundaries) in genomic DNA from 347 patients diagnosed with TNBC to determine the prevalence of deleterious mutations in this population. Two novel truncating mutations (c.758dup and c.2390del) and one previously detected truncating mutation (c.3113+5G>C) were found. In addition, five variants predicted to be protein-affecting were also identified. Our study shows that the prevalence of PALB2 germline mutations in individuals with TNBC is ∼1%, similar to the prevalence of PALB2 germline mutation of 1% in familial non-BRCA1/2 breast cancer cohorts.
authors.affiliation: School of Biomedical Sciences & Pharmacy Centre for Information-Based Medicine, University of Newcastle, Hunter Medical Research Institute, Newcastle, NSW, Australia.
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Wong-Brown
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Avery-Kiejda
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Bowden
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
mesh_terms: D001315:Australia / Q000453:epidemiology; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000151:congenital* / Q000453:epidemiology / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000235:genetics; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
keywords: PALB2; germline mutations; prevalence; triple-negative breast cancer